Nanotechnology in the diagnostic and therapy for Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder primarily characterized by ß-amyloid plaque, intraneuronal tangles, significant neuronal loss and cognitive deficit. Treatment in the early stages of the disease is crucial for preventing or perhaps reversing the neurodegeneration in the AD cases. However, none of the current diagnostic procedures are capable of early diagnosis of AD. Further, the available treatments merely provide symptomatic alleviation in AD and do not address the underlying illness. Therefore, there is no permanent cure for AD currently. Better therapeutic outcomes need the optimum drug concentration in the central nervous system (CNS) by traversing blood-brain-barrier (BBB). Nanotechnology offers enormous promise to transform the treatment and diagnostics of neurodegenerative diseases. Nanotechnology based diagnostic tools, drug delivery systems and theragnostic are capable of highly sensitive molecular detection, effective drug targeting and their combination. Significant work has been done in this area over the last decade and prospective results have been obtained in AD therapy. This review explores the various applications of nanotechnology in addressing the varied facets of AD, ranging from early detection to therapeutic interventions. This review also looks at how nanotechnology can help with the development of disease-modifying medicines, such as the delivery of anti-amyloid, anti-tau, cholinesterase inhibitors, antioxidants and hormonal drugs. In conclusion, this paper discusses the role of nanotechnology in the early detection of AD, effective drug targeting to the CNS and theragnostic applications in the management of AD.

Firearm Violence Involving Adults 65 and Older During the Novel Coronavirus Disease Pandemic.

BACKGROUND: Rates of firearm violence (FV) surged during the COVID-19 pandemic. However, there is a paucity of data regarding older adults (OAs) (≥65 years old). This study aimed to evaluate patterns of FV against OAs before and after the COVID-19 pandemic, hypothesizing decreased firearm incidents, injuries, and deaths for OAs due to restricted social movement. METHODS: Retrospective (2016-2021) data for OAs were obtained from the Gun Violence Archive. The rate of FV was weighted per 10,000 OAs using annual population data from the United States Census Bureau. Mann-Whitney U tests were performed to compare annual firearm incidence rates, number of OAs killed, and number of OAs injured from 2016-2020 to 2021. RESULTS: From 944 OA-involved shootings, 842 died in 2021. The median total firearm incidents per month per 10,000 OAs decreased in 2021 vs 2016 (.65 vs .38, P < .001), 2017 (.63 vs .38, P < .001), 2018 (.61 vs .38, P < .001), 2019 (.39 vs .38, P = .003), and 2020 (.43 vs .38, P = .012). However, there was an increased median number of OAs killed in 2021 vs 2020 (.38 vs .38, P = .009), but no difference from 2016-2019 vs 2021 (all P > .05). The median number of firearm injuries decreased from 2017 to 2021 (.21 vs .19, P = .001) and 2020 to 2021 (.19 vs .19 P < .001). DISCUSSION: Firearm incidents involving OAs decreased in 2021 compared to pre-pandemic years; however, there was a slight increase in deaths compared to 2020. This may reflect increased social isolation; however, future research is needed to understand why this occurred.

Adolescent Trauma Patients With Isolated Head Trauma and Glasgow Coma Scale 6-8: Routine Intubation?

BACKGROUND: Recent evidence suggests that routine intubation upon arrival for adults with isolated head trauma and a depressed Glasgow Coma Scale (GCS) score is associated with increased risk of morbidity and mortality. Whether these outcomes are similar within an adolescent trauma population has not been previously investigated. We hypothesized intubation upon arrival for adolescent trauma patients with isolated head trauma to be associated with a higher risk of death and prolonged length of stay (LOS). METHODS: The 2017-2019 TQIP was queried for adolescents (age 12-16) presenting after isolated blunt head trauma (abbreviated injury scale [AIS] <1 spine/chest/abdomen/upper-extremity/lower-extremity) and GCS 6-8 on arrival. Transferred patients, dead-on-arrival, and those undergoing emergent operation from the emergency department were excluded. Patients intubated within one-hour were compared to patients not intubated within one-hour. A multivariable logistic regression analysis was performed adjusting for age, sex, GCS, and AIS-grade for the head. RESULTS: From 141 patients, 73 (51.8%) were intubated upon arrival. Intubated patients had a low complication rate (5.6%). Intubated and non-intubated patients had a similar rate and mortality risk (6.8% vs 1.5%, P = .11) (OR 1.84, CI .08-43.69, P = .71) and median length of stay (LOS) (2 days vs 2 days, P = .13). DISCUSSION: Unlike adult patients, adolescents with isolated head trauma and a depressed GCS have similar outcomes if they are intubated upon arrival. Utilizing initial GCS score to determine which adolescent trauma patients with isolated head trauma should be intubated appears to be a safe practice.

A review of FDA approved drugs and their formulations for the treatment of breast cancer.

Breast cancer is one of the most diagnosed solid cancers globally. Extensive research has been going on for decades to meet the challenges of treating solid tumors with selective compounds. This article aims to summarize the therapeutic agents which are either being used or are currently under approval for use in the treatment or mitigation of breast cancer by the US FDA, to date. A structured search of bibliographic databases for previously published peer-reviewed research papers on registered molecules was explored and data was sorted in terms of various categories of drugs used in first line/adjuvant therapy for different stages of breast cancer. We included more than 300 peer-reviewed papers, including both research and reviews articles, in order to provide readers an useful comprehensive information. A list of 39 drugs are discussed along with their current status, dose protocols, mechanism of action, pharmacokinetics, possible side effects, and marketed formulations. Another interesting aspect of the article included focusing on novel formulations of these drugs which are currently in clinical trials or in the process of approval. This exhaustive review thus shall be a one-stop solution for researchers who are working in the areas of formulation development for these drugs.

Technological features of smartphone apps for physical activity promotion in patients with COPD: A systematic review.

INTRODUCTION: Low physical activity (PA) levels have a negative impact on the health status of patients with Chronic Obstructive Pulmonary Disease (COPD). Smartphone applications (apps) focused on PA promotion may mitigate this problem; however, their effectiveness depends on patient adherence, which can be influenced by the technological features of the apps. This systematic review identified the technological features of smartphone apps aiming to promote PA in patients with COPD. METHODS: A literature search was performed in the databases ACM Digital Library, IEEE Xplore, PubMed, Scopus and Web of Science. Papers including the description of a smartphone app for PA promotion in patients with COPD were included. Two researchers independently selected studies and scored the apps features based on a previously developed framework (38 possible features). RESULTS: Twenty-three studies were included and 19 apps identified, with an average of 10 technological features implemented. Eight apps could be connected to wearables to collect data. The categories 'Measuring and monitoring' and 'Support and Feedback' were present in all apps. Overall, the most implemented features were 'progress in visual format' (n = 13), 'advice on PA' (n = 14) and 'data in visual format' (n = 10). Only three apps included social features, and two included a web-based version of the app. CONCLUSIONS: The existing smartphone apps include a relatively small number of features to promote PA, which are mostly related to monitoring and providing feedback. Further research is warranted to explore the relationship between the presence/absence of specific features and the impact of interventions on patients' PA levels.

Clinical Outcome Comparison of Patients Requiring Extracorporeal Membrane Oxygenation With or Without COVID-19 Infection.

In severe COVID-19-related respiratory failure, extracorporeal membrane oxygenation (ECMO) is a useful modality that is used to provide effective oxygenation and ventilation to the patient. This descriptive study aimed to investigate and compare the outcomes between COVID-19-infected patients and patients who were not infected and required ECMO support. A retrospective study was undertaken on a cohort of 82 adult patients ([Formula: see text]18-year-old) who required venoarterial (VA-ECMO) and venovenous (VV-ECMO) ECMO between January 2019 and December 2022 in a single academic center. Patients who were cannulated for COVID-19-related respiratory failure (C-group) were compared to patients who were cannulated for non-COVID etiologies (non-group). Patients were excluded if data were missing regarding cannulation, decannulation, presenting diagnosis, and survival status. Categorical data were reported as counts and percentages, and continuous data were reported as means with 95% confidence intervals. Out of the 82 included ECMO patients, 33 (40.2%) were cannulated for COVID-related reasons, and 49 (59.8%) were cannulated for reasons other than COVID-19 infection. Compared to the non-group, the C-group had a higher in-hospital (75.8% vs. 55.1%) and overall mortality rate (78.8% vs. 61.2%). The C-group also had an average hospital length of stay (LOS) of 46.6 ± 13.2 days and an average intensive care unit (ICU) LOS of 44.1 ± 13.3 days. The non-group had an average hospital LOS of 24.8 ± 6.6 days and an average ICU LOS of 20.8 ± 5.9 days. Subgroup analysis of patients only treated with VV-ECMO yielded a greater in-hospital mortality rate for the C-group compared to the non-group (75.0% vs. 42.1%). COVID-19-infected patients may experience different morbidity and mortality rates as well as clinical presentations compared to non-COVID-infected patients when requiring ECMO support.

Real-World Safety Analysis of Paclitaxel Devices Used for the Treatment of Peripheral Artery Disease.

PURPOSE: To investigate the real-world safety of paclitaxel (PTX)-coated devices for treating lower extremity peripheral artery disease using a commercial claims database. MATERIALS AND METHODS: Data from FAIR Health, the largest commercial claims data warehouse in the United States, were used for this study. The study consisted of patients who underwent femoropopliteal revascularization procedures between January 1, 2015, and December 31, 2019, with PTX and non-PTX devices. The primary outcome was 4-year survival following treatment. The secondary outcomes included 2-year survival, 2- and 4-year freedom from amputation, and repeat revascularization. Propensity score matching was used to minimize confounding, and the Kaplan-Meier methods were used to estimate survival. RESULTS: A total of 10,832 procedures were included in the analysis, including 4,962 involving PTX devices and 5,870 involving non-PTX devices. PTX devices were associated with a reduced hazard of death following treatment at 2 and 4 years (hazard ratio [HR], 0.74 [95% confidence interval {CI}, 0.69-0.79]; P <.05, and HR, 0.89 [95% CI, 0.77-1.02]; log-rank P =.018, respectively). The risk of amputation was also lower following treatment with PTX devices than with non-PTX devices at 2 and 4 years (HR, 0.82 [95% CI, 0.76-0.87]; P =.02, and HR, 0.77 [95% CI, 0.67-0.89]; log-rank P =.01, respectively). In addition, the odds of repeat revascularization were similar with PTX and non-PTX devices at 2 and 4 years. CONCLUSIONS: In the real-world commercial claims database, no short- or long-term signal for increased mortality or amputations was observed following treatment with PTX devices.

Tele-Balint under the microscope: What really happens in Tele-Balint groups?

OBJECTIVE: Balint groups provide a safe space for clinicians to discuss difficult cases, with the aim of deepening the clinician-patient relationship and providing space for self-introspection and personal development. During this COVID-19 period, mental health clinicians need a platform to undergo professional supervision and peer learning sessions, which can be provided for by Tele-Balint sessions. This study aims to understand the workings of Balint groups in a multi-disciplinary team, through exploring the experience and perceptions of mental health clinicians in a tertiary obstetrics- and paediatrics-focused hospital in Singapore towards Tele-Balint groups, and examining if these groups can address their professional needs. METHOD: A mixed-methods study was conducted. 26 mental health clinicians who had participated in Tele-Balint groups since March 2020 completed a semi-structured questionnaire, and 12 of them were interviewed. Qualitative analysis of interview transcripts was performed. RESULTS: Qualitative analysis revealed 5 themes. The first 4: professional and personal growth of clinicians, providing emotional support to clinicians, burnout in clinicians: what contributes and what helps, and psychological safety, address whether Tele-Balint groups meet clinicians' needs. The last theme, evolution of nature of Balint groups, addresses whether Tele-Balint groups meet clinicians' needs during the time of a pandemic. CONCLUSIONS: Tele-Balint group participation was found to be beneficial in facilitating personal and professional growth, providing emotional support and preventing burnout, despite some limitations. Members should maintain flexibility towards the Balint process, in order to accommodate others who have differing needs, especially in a multi-disciplinary group.

Effects of nursing home placement on the mental health trajectories of family caregivers of people with dementia: findings from the Tele.TAnDem intervention study.

OBJECTIVES: The objective was to compare mental health trajectories between family caregivers of people with dementia (PwD) who institutionalize the care recipient (nursing home caregivers [NHC]) and caregivers who continue to provide care at home (at-home caregivers [AHC]) as well as investigate effects of a telephone-based cognitive-behavioral therapy (TEL-CBT) intervention on these trajectories. METHODS: Using linear growth models, we compared the trajectories of depressive symptoms, caregiver grief, anxiety, and quality of life (QoL) over one year (baseline - T0, 6 months - T1, and 12 months - T2) between 28 NHC and 163 AHC who had been randomized to receive 12 sessions of TEL-CBT (n = 99) or to usual care (n = 92). RESULTS: NHC reported significantly higher depression, anxiety, and caregiver grief at T0 and showed significant reductions in depression and anxiety over time compared to AHC. TEL-CBT significantly enhanced overall QoL of NHC. CONCLUSIONS: The study extends previous findings of improved mental health of family caregivers of PwD after institutionalization and emphasizes the need for interventions before nursing home placement. TEL-CBT which has previously been shown to be effective for family caregivers of PwD also seems promising for supporting NHC.Supplemental data for this article is available online at https://doi.org/10.1080/13607863.2021.2022598 .

Surgery or Endovascular Therapy for Chronic Limb-Threatening Ischemia.

BACKGROUND: Patients with chronic limb-threatening ischemia (CLTI) require revascularization to improve limb perfusion and thereby limit the risk of amputation. It is uncertain whether an initial strategy of endovascular therapy or surgical revascularization for CLTI is superior for improving limb outcomes. METHODS: In this international, randomized trial, we enrolled 1830 patients with CLTI and infrainguinal peripheral artery disease in two parallel-cohort trials. Patients who had a single segment of great saphenous vein that could be used for surgery were assigned to cohort 1. Patients who needed an alternative bypass conduit were assigned to cohort 2. The primary outcome was a composite of a major adverse limb event - which was defined as amputation above the ankle or a major limb reintervention (a new bypass graft or graft revision, thrombectomy, or thrombolysis) - or death from any cause. RESULTS: In cohort 1, after a median follow-up of 2.7 years, a primary-outcome event occurred in 302 of 709 patients (42.6%) in the surgical group and in 408 of 711 patients (57.4%) in the endovascular group (hazard ratio, 0.68; 95% confidence interval [CI], 0.59 to 0.79; P<0.001). In cohort 2, a primary-outcome event occurred in 83 of 194 patients (42.8%) in the surgical group and in 95 of 199 patients (47.7%) in the endovascular group (hazard ratio, 0.79; 95% CI, 0.58 to 1.06; P = 0.12) after a median follow-up of 1.6 years. The incidence of adverse events was similar in the two groups in the two cohorts. CONCLUSIONS: Among patients with CLTI who had an adequate great saphenous vein for surgical revascularization (cohort 1), the incidence of a major adverse limb event or death was significantly lower in the surgical group than in the endovascular group. Among the patients who lacked an adequate saphenous vein conduit (cohort 2), the outcomes in the two groups were similar. (Funded by the National Heart, Lung, and Blood Institute; BEST-CLI ClinicalTrials.gov number, NCT02060630.).

Clinical and Demographic Predictor of the Advanced Stage of Carcinoma Cervix in a Tertiary Level Hospital of Bangladesh.

Though cervical cancer is a preventable disease it is the most progressive and devastating diseases posing a threat of mortality for women of developing countries. Majority of the cases present to hospital at advanced stage when treatment is less feasible. Objective is to determine the factors associated with the advanced stage presentation to the hospital, socio-demographic factor, patterns of complications and histological types among patients with carcinoma cervix. This was an observational descriptive type of cross-sectional study carried out in the department of Obstetrics and Gynecology, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from 15 January to 27 September 2017. Women who were newly confirmed to have cervical cancer by histology were enrolled. Stages IIB and above was considered as advanced disease. The patients were interviewed face to face by the researcher for the purpose of collection of data. Then the patients were examined by the researcher for certain sings and those would be recorded in the check-list. Histopathological report was noted in data collection sheet. In this study data analysis was done by SPSS version 22.0. Total 66 clinically and histologically confirmed advanced ca-cervixes were taken up during this study. Most common stage was stage III, 49(74.2%) out of 66 population. Majority of female were found 34(51.5%) in age group 51-60. More than half of population 54(81.8%) were living with their husband and 12(18.1%) were widow at the time of study. High level of illiteracy among women and their problematic health seeking behavior for gynecological symptoms are responsible for advanced diagnosis of cervical cancer.

Impact of Epstein-Barr virus co-infection on natural acquired Plasmodium vivax antibody response.

BACKGROUND: The simultaneous infection of Plasmodium falciparum and Epstein-Barr virus (EBV) could promote the development of the aggressive endemic Burkitt's Lymphoma (eBL) in children living in P. falciparum holoendemic areas. While it is well-established that eBL is not related to other human malaria parasites, the impact of EBV infection on the generation of human malaria immunity remains largely unexplored. Considering that this highly prevalent herpesvirus establishes a lifelong persistent infection on B-cells with possible influence on malaria immunity, we hypothesized that EBV co-infection could have impact on the naturally acquired antibody responses to P. vivax, the most widespread human malaria parasite. METHODOLOGY/PRINCIPAL FINDINGS: The study design involved three cross-sectional surveys at six-month intervals (baseline, 6 and 12 months) among long-term P. vivax exposed individuals living in the Amazon rainforest. The approach focused on a group of malaria-exposed individuals whose EBV-DNA (amplification of balf-5 gene) was persistently detected in the peripheral blood (PersVDNA, n = 27), and an age-matched malaria-exposed group whose EBV-DNA could never be detected during the follow-up (NegVDNA, n = 29). During the follow-up period, the serological detection of EBV antibodies to lytic/ latent viral antigens showed that IgG antibodies to viral capsid antigen (VCA-p18) were significantly different between groups (PersVDNA > NegVDNA). A panel of blood-stage P. vivax antigens covering a wide range of immunogenicity confirmed that in general PersVDNA group showed low levels of antibodies as compared with NegVDNA. Interestingly, more significant differences were observed to a novel DBPII immunogen, named DEKnull-2, which has been associated with long-term neutralizing antibody response. Differences between groups were less pronounced with blood-stage antigens (such as MSP1-19) whose levels can fluctuate according to malaria transmission. CONCLUSIONS/SIGNIFICANCE: In a proof-of-concept study we provide evidence that a persistent detection of EBV-DNA in peripheral blood of adults in a P. vivax semi-immune population may impact the long-term immune response to major malaria vaccine candidates.

Antibody response to a new member of the DBL family (EBP2) after a brief Plasmodium vivax exposure.

Plasmodium vivax blood-stage invasion into reticulocyte is critical for parasite development. Thus, validation of novel parasite invasion ligands is essential for malaria vaccine development. Recently, we demonstrated that EBP2, a Duffy binding protein (DBP) paralog, is antigenically distinct from DBP and could not be functionally inhibited by anti-DBP antibodies. Here, we took advantage of a small outbreak of P.vivax malaria, located in a non-malarious area of Brazil, to investigate for the first time IgM/IgG antibodies against EBP2 and DEKnull-2 (an engineering DBPII vaccine) among individuals who had their first and brief exposure to P.vivax (16 cases and 22 non-cases). Our experimental approach included 4 cross sectional surveys at 3-month interval (12-month follow-up). The results demonstrated that while a brief initial P.vivax infection was not efficient to induce IgM/ IgG antibodies to either EBP2 or DEKnull-2, IgG antibodies against DEKnull-2 (but not EBP2) were boosted by recurrent blood-stage infections following treatment. Of interest, in most recurrent P. vivax infections (4 out of 6 patients) DEKnull-2 IgG antibodies were sustained for 6 to 12 months. Polymorphisms in the ebp2 gene does not seem to explain EBP2 low immunogenicity as the ebp2 allele associated with the P.vivax outbreak presented high identity to the original EBP2 isolate used as recombinant protein. Although EBP2 antibodies were barely detectable after a primary episode of P.vivax infection, EBP2 was highly recognized by serum IgG from long-term malaria-exposed Amazonians (range from 35 to 92% according to previous malaria episodes). Taken together, the results showed that individuals with a single and brief exposure to P.vivax infection develop very low anti-EBP2 antibodies, which tend to increase after long-term malaria exposure. Finally, the findings highlighted the potential of DEKnull-2 as a vaccine candidate, as in non-immune individuals anti-DEKnull-2 IgG antibodies were boosted even after a brief exposure to P.vivax blood stages.

Surface plasmon resonance: A promising approach for label-free early cancer diagnosis.

Cancer is the second leading cause of death worldwide after cardiovascular disease. The major cause of high mortality is delayed detection. Therefore, detection at an early stage followed by early treatment can mitigate morbidity as well as mortality. The utilization of biomarker-based detection tools helps in early-stage recognition. Fortunately, biomarkers indicating disease status are released in to the circulation. These include traditional marker proteins as well as exosomes, micro-RNA (miRNA) and circulating tumor DNA (ct-DNA). Biosensors are biological and chemical reaction devices that generate signals based on analyte concentration. Due to analyte binding, these devices demonstrate high sensitivity and specificity. This review examines the use of surface plasmon resonance (SPR)-based sensors in the diagnosis of various cancer including those of the breast, prostate, lung, ovary, cervix and pancreas. SPR is a label-free, real-time and non-invasive optical biosensing technology representing a novel diagnostic tool in cancer detection.

The Current Landscape and Emerging Applications for Real-World Data in Diagnostics and Clinical Decision Support and its Impact on Regulatory Decision Making.

Real-world data (RWD) and real-world evidence (RWE) are becoming essential tools for informing regulatory decision making in health care and offer an opportunity for all stakeholders in the healthcare ecosystem to evaluate medical products throughout their lifecycle. Although considerable interest has been given to regulatory decisions supported by RWE for treatment authorization, especially in rare diseases, less attention has been given to RWD/RWE related to in vitro diagnostic (IVD) products and clinical decision support systems (CDSS). This review examines current regulatory practices in relation to IVD product development and discusses the use of CDSS in assisting clinicians to retrieve, filter, and analyze patient data in support of complex decisions regarding diagnosis and treatment. The review then explores how utilizing RWD could augment regulatory body understanding of test performance, clinical outcomes, and benefit-risk profiles, and how RWD could be leveraged to augment CDSS and improve safety, quality, and efficiency of healthcare practices. Whereas we present examples of RWD assisting in the regulation of IVDs and CDSS, we also highlight key challenges within the current healthcare system which are impeding the potential of RWE to be fully realized. These challenges include issues such as data availability, reliability, accessibility, harmonization, and interoperability, often for reasons specific to diagnostics. Finally, we review ways that these challenges are actively being addressed and discuss how private-public collaborations and the implementation of standardized language and protocols are working toward producing more robust RWD and RWE to support regulatory decision making.

MiADMSA abrogates sodium tungstate-induced oxidative stress in rats.

Tungsten (W) and its compounds have emerged as a relatively new area of environmental health concern in the last decade. Tungsten is environmentally benign due to its increasing use in armour-piercing munitions and as a replacement for lead in other ammunition. It has also been identified in various hazardous waste sites and therefore been proposed for inclusion in the Environmental Protection Agency National Priorities List. The major objective of this study was to evaluate the therapeutic efficacy of orally administered monoisoamyl 2, 3-dimercaptosuccinic acid (MiADMSA) against tungstate induced oxidative injury in blood, liver and kidneys of male Wistar rats. MiADMSA, a thiol chelator has gained wide recognition recently as a future chelating drug of choice specifically for arsenic and was chosen for this study as tungstate ions too have an affinity toward the -SH group thus, being less bioavailable in the body. We determined the effects of MiADMSA (50 mg/kg, p.o.) against sodium tungstate (500 ppm in drinking water, daily for 28 days) induced biochemical changes indicative of oxidative stress in blood, and other soft tissues of of male Wistar rats. Tungsten exposure led to an increased levels of Reactive Oxygen Species (ROS) in liver, kidney, spleen and blood accompanied also by an increase in TBARS levels. The GSH: GSSG ratio also showed a decrease on sodium tungstate intoxication. Treatment with MiADMSA restored most of the sodium tungstate-induced alterations in the biomarkers suggestive of oxidative stress. These preliminary results led us to conclude that sub-acute exposure to tungstate-induced oxidative stress could be effectively reduced by the administration of MiADMSA and thus might be a promising antidote for studying in detail its efficacy in reducing body tungstate burden and its excretion post tungstate exposure.

Multiplexed Microsphere-Based Flow Cytometric Assay to Assess Strain Transcending Antibodies to Plasmodium vivax Duffy Binding Protein II Reveals an Efficient Tool to Identify Binding-Inhibitory Antibody Responders.

Malaria remains a major public health problem worldwide, and Plasmodium vivax is the most widely distributed malaria parasite. Naturally acquired binding inhibitory antibodies (BIAbs) to region II of the Duffy binding protein (DBPII), a P. vivax ligand that is critical for reticulocyte invasion, are associated with a reduced risk of clinical malaria. Owing to methodological issues in evaluating antibodies that inhibit the DBPII-DARC interaction, a limited number of studies have investigated DBPII BIAbs in P. vivax-exposed populations. Based on the assumption that individuals with a consistent BIAb response are characterized by strain-transcending immune responses, we hypothesized that detecting broadly reactive DBPII antibodies would indicate the presence of BIAb response. By taking advantage of an engineered DBPII immunogen targeting conserved DBPII neutralizing epitopes (DEKnull-2), we standardized a multiplex flow cytometry-based serological assay to detect broadly neutralizing IgG antibodies. For this study, a standard in vitro cytoadherence assay with COS-7 cells expressing DBPII was used to test for DBPII BIAb response in long-term P. vivax-exposed Amazonian individuals. Taken together, the results demonstrate that this DBPII-based multiplex assay facilitates identifying DBPII BIAb carriers. Of relevance, the ability of the multiplex assay to identify BIAb responders was highly accurate when the positivity for all antigens was considered. In conclusion, the standardized DBPII-based flow cytometric assay confirmed that DBPII-BIAb activity was associated with the breadth rather than the magnitude of anti-DBPII antibodies. Altogether, our results suggest that multiplex detection of broadly DBPII-reactive antibodies facilitates preliminary screening of BIAb responders.

Organic-Molecule-Based Fluorescent Chemosensor for Nerve Agents and Organophosphorus Pesticides.

Organophosphorus (OP) compounds are typically a broad class of compounds that possess various uses such as insecticides, pesticides, etc. One of the most evil utilizations of these compounds is as chemical warfare agents, which pose a greater threat than biological weapons because of their ease of access. OP compounds are highly toxic compounds that cause irreversible inhibition of enzyme acetylcholinesterase, which is essential for hydrolysis of neurotransmitter acetylcholine, leading to series of neurological disorders and even death. Due to the extensive use of these organophosphorus compounds in agriculture, there is an increase in the environmental burden of these toxic chemicals, with severe environmental consequences. Hence, the rapid and sensitive, selective, real-time detection of OP compounds is very much required in terms of environmental protection, health, and survival. Several techniques have been developed over a few decades to easily detect them, but still, numerous challenges and problems remain to be solved. Major advancement has been observed in the development of sensors using the spectroscopic technique over recent years because of the advantages offered over other techniques, which we focus on in the presented review.

Nanodiamonds: A Versatile Drug-Delivery System in the Recent Therapeutics Scenario.

Nanodiamonds (ND) belong to the nano-carbon family, which involves several synthesis, post-synthesis methods, and other modifications for ND preparation. NDs have played vital role both inside and outside of medicine in recent years. The study of NDs has stated in early 1960s, NDs are smaller particles with a size of about 4-5 nm with confined size distribution, large-scale synthesis at lower costs relying on the carbon explosives ignition, apparent surface functional design along with bio-conjugation and extreme biocompatibility. It has been predicted that the ND's magnetic characteristics will contribute to the up-growth of various therapeutic promoters for delivery vehicles, diagnostic probes, gene therapy, tissue scaffolds, anti-bacterial and anti-viral treatments, and devices like nano-robots. Furthermore, the wide applications of biotechnology have displayed the potential usage of NDs in certain bioanalytical needs like fluorescent bio labeling through fluorescent and protein purification of proteins. In this current review, the determination of ND's design, property, classes, constancy, organization, surface modification, biocompatibility, and its applications in the biomedical field have penned. The usage of ND as anti-neoplastic agents and in other health related formulations have displayed exceptional results for future growth. Additionally, NDs provide other functionalities such as production of biodegradable surgical devices of bone, the assassination of drug resistant microbes and viruses, tissue engineering scaffolds, and aids in the delivery of genetic matter into the nucleus of cells.

Alpha-Lipoic Acid Protects Co-Exposure to Lead and Zinc Oxide Nanoparticles Induced Neuro, Immuno and Male Reproductive Toxicity in Rats.

We evaluated the neuro-, immuno-, and male reproductive toxicity of zinc oxide nanoparticles (ZnO NPs) alone and in combination with lead acetate. We also studied the therapeutic role of α-lipoic acid postexposure. Lead (10 mg/kg, body weight), ZnO NPs (100 mg/kg, bwt) alone, and their combination were administered orally in Wistar rats for 28 days, followed by the administration of α-lipoic acid (15 mg/kg, bwt) for the next 15 days. Our results demonstrated protective effects of α-lipoic acid on lead and ZnO NP-induced biochemical alterations in neurological, immunological, and male reproductive organs in rats. The altered levels of blood δ-aminolevulinic acid dehydratase (ALAD), immunoglobulins (IgA, IgG, IgM, and IgE), interleukins (IL-1ß, IL-4, and IL-6), caspase-3, and tumor necrosis factor (TNF-α) were attenuated by lipoic acid treatment. Lead and ZnO NP-induced oxidative stress was decreased by lipoic acid treatment, while a moderate recovery in the normal histoarchitecture of the brain section (cortex and hippocampus) and testes further confirmed the neuro- and male reproductive toxicity of lead and ZnO NPs. We also observed a significant decrease in the blood metal content in the animals treated with lipoic acid compared to the lead-administered group, indicating the moderate chelating property of lipoic acid. It may thus be concluded that lipoic acid might be a promising protective agent against lead and ZnO NP-induced alterations in the neurological, immunological, and reproductive parameters.